[Cardiovascular safety of new drugs for the acute and preventive treatment of migraine: gepants and ditans]. / Seguridad cardiovascular de los nuevos fármacos para el tratamiento agudo y preventivo de la migraña: gepantes y ditanes.

INTRODUCTION: Migraine is a prevalent neurological condition characterised by disabling headache attacks. In recent decades, new drugs have been developed specifically for the acute and preventive treatment of migraine based on its pathophysiology. These include calcitonin gene-related peptide (CGRP) antagonists (CGRP) (gepants) and selective serotoninergic 5-HT1F receptor agonists (ditans). CGRP is a neuropeptide released by trigeminal terminals that acts as a vasodilator, causes neurogenic inflammation and thus generates pain and sensitisation in migraine. It also has a powerful vasodilatory action and is involved in cardiovascular regulation, which is why numerous studies are under way to assess the vascular safety of acting against CGRP. The high selectivity of ditans for the serotoninergic 5-HT1F receptor with a low affinity for other serotoninergic receptors seems to translate into little or no vasoconstrictor effect, which is mediated by the activation of 5-HT1B receptors. DEVELOPMENT: The aim of our study is to review the cardiovascular safety demonstrated by these new drugs for the treatment of migraine by analysing the evidence published to date. We conducted a literature search in the PubMed database and a review of clinical trials published at clinicaltrial.gov. We included literature reviews, meta-analyses and clinical trials in English and Spanish. We analysed reported cardiovascular adverse effects. CONCLUSIONS: Based on the results published to date, we can conclude that the cardiovascular safety profile of these new treatments is favourable. Longer-term safety studies are needed to confirm these results.

TITLE: Seguridad cardiovascular de los nuevos fármacos para el tratamiento agudo y preventivo de la migraña: gepantes y ditanes.Introducción. La migraña es una patología neurológica prevalente caracterizada por ataques de cefalea incapacitantes. En las últimas décadas se han desarrollado nuevos fármacos específicos para el tratamiento agudo y preventivo de la migraña basados en su fisiopatología. Entre éstos se encuentran los antagonistas del péptido relacionado con el gen de la calcitonina (CGRP) (gepantes) y los agonistas selectivos del receptor serotoninérgico 5-HT1F (ditanes). El CGRP es un neuropéptido liberado por los terminales trigeminales que actúa como vasodilatador, provoca inflamación neurógena y, con ello, generación del dolor y sensibilización en la migraña. Posee, además, una potente acción vasodilatadora y participa en la regulación cardiovascular, razón por la cual se están llevando a cabo numerosos estudios que evalúan la seguridad vascular de actuar contra el CGRP. La alta selectividad de los ditanes para el receptor serotoninérgico 5-HT1F con una baja afinidad para otros receptores serotoninérgicos parece traducirse en un bajo o nulo efecto vasoconstrictor, que es mediado por la activación de los receptores 5-HT1B. Desarrollo. Nuestro objetivo es revisar la seguridad cardiovascular demostrada por estos nuevos fármacos para el tratamiento de la migraña analizando la evidencia publicada. Realizamos una búsqueda bibliográfica en la base de datos PubMed y una revisión de los ensayos clínicos publicados en clinicaltrial.gov. Incluimos revisiones bibliográficas, metaanálisis y ensayos clínicos en español e inglés. Analizamos los efectos adversos cardiovasculares informados. Conclusiones. Basándonos en los resultados hasta ahora publicados, podemos concluir que el perfil de seguridad cardiovascular de estos nuevos tratamientos es favorable. Para confirmar estos resultados son necesarios estudios de seguridad a más largo plazo.

[Acute intracranial hypertension]. / Hipertensión intracraneal aguda.

Acute intracranial hypertension is a syndrome with multiple etiologies. Diagnosis and treatment must be performed urgently to save the patient's life and prevent the development of significant disabilities. The appearance of this syndrome is due to intracraincreased volumes and -in turn- the pressure of the intracranial contents, either through an increase in the physiological components (blood, cerebrospinal fluid and brain parenchyma), or through the appearance of a volume in the form of added mass. The underlying brain edema in this condition may be of several types: cytotoxic, vasogenic, interstitial, or hydrostatic. Increased intracranial pressure decreases cerebral perfusion pressure, creating a vicious cycle because of the resulting cerebral ischemia, which progressively increases cerebral blood volume by decreasing resistance and further increases intracranial pressure. Treatment depends on the etiology and will generally require medical and surgical care. Patient management is usually carried out in neurocritical units and involves intracranial pressure monitoring to guide treatment. Correction of all hemostasis disorders is also crucial to patient survival.

Oxcarbazepine monotherapy in carbamazepine-unresponsive trigeminal neuralgia.

The objective of this prospective open-label study was to evaluate the efficacy and tolerability of oxcarbazepine in trigeminal neuralgia (TN) unresponsive to treatment with the standard antiepileptic drug, carbamazepine. Thirty-five patients with idiopathic TN, who underwent treatment with oxcarbazepine monotherapy for at least 12 weeks, were studied. Pain was assessed using mean pain frequency, responder rate, pain-free patients and clinical global impression. The mean maintenance dose was 773.7 mg/day. There was a significant decrease in the mean of the main scores following 12 weeks of treatment (p<0.05) compared with baseline. Oxcarbazepine was effective from the first month of treatment. There was a significant reduction in pain frequency, leading to improvements in patient satisfaction. In general, oxcarbazepine was well tolerated. Oxcarbazepine appears to be an important alternative therapeutic approach for patients affected by TN. This study adds to the existing literature arriving at the same findings.

Seguridad cardiovascular de los nuevos fármacos para el tratamiento agudo y preventivo de la migraña: gepantes y ditanes / Cardiovascular safety of new drugs for the acute and preventive treatment of migraine: gepants and ditans

Introducción: La migraña es una patología neurológica prevalente caracterizada por ataques de cefalea incapacitantes. En las últimas décadas se han desarrollado nuevos fármacos específicos para el tratamiento agudo y preventivo de la migraña basados en su fisiopatología. Entre éstos se encuentran los antagonistas del péptido relacionado con el gen de la calcitonina (CGRP) (gepantes) y los agonistas selectivos del receptor serotoninérgico 5-HT1F (ditanes). El CGRP es un neuropéptido liberado por los terminales trigeminales que actúa como vasodilatador, provoca inflamación neurógena y, con ello, generación del dolor y sensibilización en la migraña. Posee, además, una potente acción vasodilatadora y participa en la regulación cardiovascular, razón por la cual se están llevando a cabo numerosos estudios que evalúan la seguridad vascular de actuar contra el CGRP. La alta selectividad de los ditanes para el receptor serotoninérgico 5-HT1F con una baja afinidad para otros receptores serotoninérgicos parece traducirse en un bajo o nulo efecto vasoconstrictor, que es mediado por la activación de los receptores 5-HT1B. Desarrollo: Nuestro objetivo es revisar la seguridad cardiovascular demostrada por estos nuevos fármacos para el tratamiento de la migraña analizando la evidencia publicada. Realizamos una búsqueda bibliográfica en la base de datos PubMed y una revisión de los ensayos clínicos publicados en clinicaltrial.gov. Incluimos revisiones bibliográficas, metaanálisis y ensayos clínicos en español e inglés. Analizamos los efectos adversos cardiovasculares informados. Conclusiones: Basándonos en los resultados hasta ahora publicados, podemos concluir que el perfil de seguridad cardiovascular de estos nuevos tratamientos es favorable. Para confirmar estos resultados son necesarios estudios de seguridad a más largo plazo.(AU)

Introduction: Migraine is a prevalent neurological condition characterised by disabling headache attacks. In recent decades, new drugs have been developed specifically for the acute and preventive treatment of migraine based on its pathophysiology. These include calcitonin gene-related peptide (CGRP) antagonists (CGRP) (gepants) and selective serotoninergic 5-HT1F receptor agonists (ditans). CGRP is a neuropeptide released by trigeminal terminals that acts as a vasodilator, causes neurogenic inflammation and thus generates pain and sensitisation in migraine. It also has a powerful vasodilatory action and is involved in cardiovascular regulation, which is why numerous studies are under way to assess the vascular safety of acting against CGRP. The high selectivity of ditans for the serotoninergic 5-HT1F receptor with a low affinity for other serotoninergic receptors seems to translate into little or no vasoconstrictor effect, which is mediated by the activation of 5-HT1B receptors. Development: The aim of our study is to review the cardiovascular safety demonstrated by these new drugs for the treatment of migraine by analysing the evidence published to date. We conducted a literature search in the PubMed database and a review of clinical trials published at clinicaltrial.gov. We included literature reviews, meta-analyses and clinical trials in English and Spanish. We analysed reported cardiovascular adverse effects. Conclusions: Based on the results published to date, we can conclude that the cardiovascular safety profile of these new treatments is favourable. Longer-term safety studies are needed to confirm these results.(AU)

[Topiramate in comorbid disorders: epilepsy and migraine]. / Topiramato en enfermedades comórbidas: epilepsia y migraña.

INTRODUCTION: With relative frequency epilepsy and migraine are associated in a same patient. Some times it is difficult to distinguish an attack of others. Reason why it would be of utility to have a treatment effective in both pathologies. It is tried to study in patients with this comorbidity, how of effective it is a drug indicated in the two pathologies, as it is topiramate. PATIENTS AND METHODS: An observational, longitudinal and prospective study is made, where 15 patients are recruited with this association, and which they were treated with topiramate. They are revaluated at three and six months of treatment. RESULTS: Significant differences are obtained (p < 0.05) in all the studied variables (severity and duration of the migraine attacks and frequency of the migraine and epileptic attacks), with a medium dose of 100 mg/day of topiramate, at the end of the study. Not serious adverse effects were observed. CONCLUSIONS: Topiramate in monotherapy seems to be a suitable treatment in patients who undergo epileptic and migrainous attacks jointly.

Intracranial Hodgkin's disease. Report of two cases.

Two cases of Hodgkin's disease are described; one was intracerebrally located and the other one extended to bone, dura mater and cerebral parenchyma. The classification of the different types of intracranial Hodgkin's disease is reviewed, and the role of Computed Tomography and surgery in the management of this pathology is emphasized.

Neuromodulators and therapeutic targets in neuropathic pain: from molecules to man.

Neuropathic pain is a phenomenon characterized by a high population prevalence by possessing several etiologies. In contrast to nociceptive pain, painful signals in neuropathic pain are originated in the nervous system, present poor responses to conventional treatments and may worsen the quality of life. Antiepileptic drugs are increasingly used for different purposes including migraine, neuropathic pain, tremor or psychiatric disorders and they have started to be called neuromodulators. These drugs may act on very different targets such as sodium, potassium or calcium channels, purinergic, GABAergic, glutamatergic or vanilloid receptors and different cytokines including IL-6 or TNF, each if which may be important in managing some aspects of neuropathic pain. Antiepileptic drugs have demonstrated effectiveness in the treatment of this pathology, and owing to the important development of these drugs in the last years, they may become a very effective tool. On the other hand, the increasing knowledge of the pathophysiology of nociception is leading to new channels and receptors as potential targets for treatment. In this paper we try to review the different potential therapeutic targets and role of antiepileptic drugs in the treatment of this pathology.

[Worsening of migraine symptoms due to giant pineal cyst apoplexy]. / Agravamiento de un cuadro migrañoso por apoplejía de un quiste pineal gigante.

INTRODUCTION: Although the association between headaches and pineal gland cysts has been suggested on a number of occasions, no precise evidence of exactly what this relation involves has been produced to date. It is known, however, that a cyst in the pineal gland can bring on or worsen headaches, especially if it is large or there has been bleeding, due to obstructive compromise in the third ventricle and the resulting hydrocephalus that is produced. CASE REPORT: A 15 years-old male who had suffered from migraine from the age of 6 years and who suddenly experienced a worsening of his headaches, both as regards their frequency and their intensity, over the previous days; no known precipitating factor appeared to be involved. Magnetic resonance imaging of the brain revealed the presence of a giant cyst in the pineal gland, with a notable amount of blood inside it, which was producing an obstructive hydrocephalus. The decision was made to resort to surgical treatment, with resection of the cyst and placement of a shunt valve. As a result the patient's headaches improved greatly and this improvement continued throughout a six-month follow-up. CONCLUSIONS: Worsening of a headache, in this case migraine, for no apparent cause must make us consider secondary processes, although they may be as rare as the one described here.

[Headache among oldest old (+75 years): findings from 736 consecutive subjects in outpatient neurological clinic]. / Cefalea en los muy ancianos (75 años y más): resultados de una serie consecutiva ambulatoria de 736 pacientes.

INTRODUCTION: Although the elderly generally suffer less often from headache, many authors suggest that symptomatic headache and concomitant diseases could be more frequent. We performed a retrospective chart review of oldest old (+75 years) patients who seek medical attention from headache. METHODS: A retrospective chart review (9 years) was carried on all oldest old subjects (> or =75 years) who were studied from outpatient neurological clinic. Headache diagnosis was made according to the new classification of the International Headache Society. RESULTS: Seven hundred and thirty six patients were reviewed. 77,7% were females. Median age was 81,5 years (standard desviation: 5,3). This subjects were 1,7% from all consultations. 89,4% subjects suffered primary headaches. Tensional headache was the most frequent diagnosis. Serious causes were unusual. No patients had headache relationship with neoplasm or infections diseases. Only four subjects (0,6%) had temporal arteritis. Subjects with 81 years and more had less migraine and more Arnold's neuralgia (Greater occipital neuralgia). CONCLUSIONS: In our study, headache among oldest old had relationship with benign causes like tensional headache. Although serious causes like neoplasm or infections disease were not detected in our patients, temporal arteritis could be an important cause to screen from outpatient neurological clinic.

[Zonisamide in refractory essential tremor]. / Zonisamida en el temblor esencial refractario.

INTRODUCTION: Essential tremor is one of the most frequent movement disorders. It is characterized by postural and action tremor that may affect different regions of the body. Among current treatments propranolol and primidone are included. However, these two drugs have demonstrated a limited efficacy and several adverse events. Additionally, they are contraindicated in patients with cardiac insufficiency and several respiratory diseases. New antiepileptic drugs are revealing as a possibility in the treatment of this disease. AIM. To evaluate efficacy and tolerability of zonisamide in the treatment of essential tremor. PATIENTS AND METHODS: We perform a retrospective study about 13 patients with essential tremor refractory to an average of 2.8 drugs. Age, sex, zonisamide dosage, adverse events, duration and response to the treatment before and after the treatment were collected and analysed. Average zonisamide dosage was 215 mg/day and average duration of the treatment was 121 days. RESULTS: Nine of 13 patients included in our study experienced a good response. A positive response was understood as a decrease on the limitation of daily activities and an improvement on neurological examination. Zonisamide was well tolerated and no patient abandoned the study for this reason. CONCLUSIONS: Our data suggest that zonisamide is effective and well tolerated in the treatment of essential tremor. Placebo-controlled and bigger studies are warranted to confirm these results.

[Rotigotine in the treatment of Parkinson's disease. A study on a sample of 150 patients]. / Rotigotina en el tratamiento de la enfermedad de Parkinson. Experiencia sobre una muestra de 150 pacientes.

INTRODUCTION: Rotigotine is a non-ergot dopamine agonist that has become the first treatment for Parkinson's disease formulated as a transdermal release system. Its side effects are very similar to those of other dopamine agonists, as well as those deriving from the site of application, while its advantages include a once-daily administration, the absence of interactions with foods and steady levels in plasma. AIM: To determine the frequency of and reasons for withdrawing rotigotine in 150 consecutive patients diagnosed with Parkinson's disease. PATIENTS AND METHODS: A retrospective analysis was carried out using the database at our Movement Disorders Unit in order to identify the first 150 patients who were treated with rotigotine. Only patients with Parkinson's disease who were free of intracranial lesions, psychiatric pathologies or dementia were eligible for inclusion in the sample. Patients were evaluated before and at two, four and six months after beginning treatment with rotigotine. RESULTS: In all, 85 males and 65 females were identified. A total of 110 of them had previously been treated with dopamine agonists. Although 12% of the patients dropped out, 88% of them continued the treatment. The reasons for withdrawing were worsening of the clinical condition (12 patients), lack of effectiveness (three patients), drowsiness (two patients) and dyskinesias (one patient). CONCLUSIONS: Rotigotine is safe and effective as medication in the treatment of Parkinson's disease. The fact that most of the drop-outs were due to a worsening of the clinical signs and symptoms after changing from another dopamine agonist suggests the need for an equivalence between other agonists and rotigotine.

Prevalencia de síntomas neurológicos asociados a la fibromialgia / Prevalence of neurological symptoms associated with fibromyalgia

Introducción: La fibromialgia se puede considerar un síndrome del que el síntoma más frecuente, y de hecho único criterio diagnóstico, es el dolor. Sin embargo, como cuadro sindrómico que es, engloba muchos otros síntomas y signos, posiblemente igualmente importantes y, a veces, tan incapacitantes como el propio dolor. Dentro de todos ellos, los relacionados con la esfera neurológica pueden ser fundamentales para comprender el estado general que padecen los pacientes. Material y métodos: Se diseñó y realizó una encuesta a pacientes con diagnóstico previo de fibromialgia, interrogando de forma específica por síntomas o signos neuropsicológicos asociados a su enfermedad, así como la posibilidad de estar recibiendo tratamiento para ellos. Además, indagamos por los posibles determinantes del origen de la enfermedad y, por último, también por la opinión de los pacientes acerca del posible origen de su problema, la fibromialgia. Resultados: Recogimos encuestas hasta completar un total de 100 pacientes. Se observó un alto porcentaje de síntomas relacionados con el sistema nervioso en estos pacientes, y la mayoría de los síntomas por los que se preguntó en el momento de la encuesta, se encontraba por encima del 50% de los pacientes. Por otro lado, casi dos terceras partes de los pacientes relacionaron el origen de su enfermedad con algún factor estresante o desencadenante. Sobre el origen de la fibromialgia, la respuesta más repetida por los pacientes fue de causa desconocida, seguido del posible origen reumatológico y, en tercer lugar, el neurológico. Conclusiones: Diversos síntomas neurológicos se asocian con alta frecuencia a su enfermedad, según los propios pacientes. Todos los clínicos involucrados en el estudio y tratamiento de este cuadro deberían tener en cuenta la participación de estos síntomas relacionados con la esfera neurológica, por su alta proporción y trascendencia, según lo refieren los pacientes con fibromialgia (AU)

Introduction: Fibromyalgia can be considered a syndrome. The most frequent symptom and, in fact, the only diagnostic criterion is pain. Nevertheless, as a syndromic picture, fibromyalgia includes many other symptoms and signs, which are equally important and possibly sometimes as disabling as pain. Among all of these symptoms and signs, those related to the neurological sphere may be fundamental to understanding patients’ general state. Material and methods: We designed and performed a survey of patients with a prior diagnosis of fibromyalgia with specific items on neuropsychological signs or symptoms associated with this disease, as well as the possibility of receiving treatment for these manifestations. In addition, we enquired about the possible triggering factors of the disease, and the patient’s opinion on the possible cause of the fibromyalgia. Results: One hundred surveys were completed. A high percentage of the symptoms were related to the nervous system and, at the time of the survey, these symptoms were reported by over 50% of the patients. Almost two-thirds of the patients related the onset of their disease with a stress or triggering factor. On the cause of the fibromyalgia, the most frequent response was that the fibromyalgia was of unknown cause, followed by a possible rheumatologic origin, and thirdly, of a neurological origin. Conclusions: Patients with fibromyalgia reported a high frequency of associated neurological symptoms. Consequently, all clinicians involved in the study and treatment of fibromyalgia should bear in mind the role of neurological symptoms in this syndrome (AU)